Tadeusz Przewłocki

Altered Fibrin Clot Structure/Function in Patients With Cryptogenic Ischemic Stroke

Background and Purpose— We tested the hypothesis that fibrin structure/function is unfavorably altered in patients with cryptogenic ischemic stroke. Methods— Ex vivo plasma fibrin clot permeability, turbidimetry, and efficiency of fibrinolysis were determined in 89 patients with patent foramen ovale (PFO) and a history of first-ever stroke, 58 patients with first-ever stroke and no PFO, and 120 healthy controls. Results— Stroke patients, evaluated 3 to 19 months after the event, and controls did not differ with regard to age, sex, smoking, and fibrinogen. Stroke patients with or without PFO had lower clot permeability (P<0.0001), faster fibrin polymerization (P<0.0001), prolonged clot lysis time (P<0.0001), higher maximum D-dimer levels released from clots (P<0.0001), and maximum rate of D-dimer release (P=0.02) than controls. Time from stroke occurrence showed no association with any clot variables. Scanning electron microscopy of fibrin clots showed increased fiber diameter and density in stroke patients. Clots from stroke patients with PFO were more permeable and showed shorter lysis time compared to those without PFO, and this was related to lower proportion of smokers in the former group. Conclusions— Altered fibrin clot structure and resistance to fibrinolysis are associated with cryptogenic stroke.

Determinants of immediate and long-term results of subclavian and innominate artery angioplasty

Background: Percutaneous angioplasty (PTA) is widely used in the treatment of subclavian/innominate artery obstruction, but factors of long‐term PTA outcome are poorly understood. Our aim was to evaluate the efficiency of PTA on symptom resolution and identify determinants of long‐term outcome. Methods and Results: Seventy‐six lesions were treated in 75 patients (58.7% men) aged 60 ± 8.5 years. PTA was successful in 70 (93.3%) patients, including 58/58 (100%) stenotic lesions and 13/18 (72.2%) occlusions. The mean stenosis grade (QCA) was reduced from 78.9% ± 16.6% to 13.5% ± 10.7% (P < 0.01). A great majority of lesions (87.1%) were stented. In 5 (7.1%) high‐risk lesions a proximal or distal neuroprotection system was used. There were no strokes or embolic events. Minor complications occurred in 7 (9.3%) cases. Fifty‐seven (89%) of 64 symptomatic patients had complete symptom resolution. The mean follow‐up was 24.4 ± 15.5 months (up to 66 months). Ten restenoses (15.6%), including 9 (13.8%) in‐stent restenoses and 1 (16.7%) restenosis after balloon angioplasty, were diagnosed in 64 patients and followed up for at least 6 months. Nine symptomatic restenoses were successfully treated with repeated angioplasty. Cox multivariable analysis revealed the following independent predictors of restenosis: implantation of more than one stent (P = 0.005), low stent diameter (P = 0.088), and postprocedural systolic blood pressure difference between upper extremities (P = 0.044). Conclusions: PTA is a safe and effective method for the treatment of the subclavian/innominate artery obstruction and leads to symptom resolution in majority of patients. Restenosis is not frequent and it can be effectively treated with repeat angioplasty. Low stent diameter, implantation of two stents, and upper limb systolic blood pressure difference are independent predictors of restenosis.

Carotid artery stenting with patient- and lesion-tailored selection of the neuroprotection system and stent type: early and 5-year results from a prospective academic registry of 535 consecutive procedures (TARGET-CAS).

Purpose: To develop and prospectively evaluate the safety and efficacy of an algorithm for tailoring neuroprotection devices (NPD) and stent types to the patient/lesion in carotid artery stenting (CAS). Methods: From November 2002 to October 2007, 499 patients (360 men; mean age 65.2±8.4 years, range 36–88) were prospectively enrolled in a safety and efficacy study of tailored CAS using proximal (flow blockade or reversal) or distal (filters or occlusion) NPDs and closed- or open-cell self-expanding stents. Of the 535 lesions treated in the study, 175 (32.7%) were “high risk” by morphology. Half (50.1%) the patients were symptomatic. Results: A quarter (137, 25.6%) of the procedures were performed under proximal protection and the remainder (398, 74.4%) with distal NPDs; the direct stenting rate was 66.9%. High-risk lesions were treated predominantly with a proximal NPD and closed-cell stent (77.1% and 82.9%, respectively) and less frequently by direct stenting (37.1%, p<0.0001 versus non-high-risk lesions). The in-hospital death/stroke rate was 2.0% (95% CI 0.85% to 3.23%), and the death/major stroke rate was 0.7% (95% CI 0.02% to 1.48%). There were no myocardial infarctions, but there was 1 (0.2%) further death within 30 days. With the tailored approach, symptom status and high-risk lesion morphology were not risk factors for an adverse outcome after CAS; only age >75 years (p<0.001) was a predictor of short-term death. Long-term survival (95.4% at 1 and 88.3% at 5 years) was similar for symptomatic versus asymptomatic patients, direct stenting versus predilation, and closed-vs. open-cell stent design; only coronary artery disease adversely impacted survival (p=0.04). The rates of freedom from death/ipsilateral stroke were 94.9% at 1 year and 85.9% at 5 years. Conclusion: Tailored CAS is associated with a low complication rate and high long-term efficacy. CAS operators should have a practical knowledge of different NPDs, including at least one proximal type.

Assessment of myocardial perfusion in patients with coronary artery disease. Comparison of myocardial contrast echocardiography and 99mTc MIBI single photon emission computed tomography.

BACKGROUND Myocardial perfusion (MP) can be assessed in real time when using a low mechanical index (MI) and harmonic imaging following an intravenous injection of contrast agent. The aim of the study was to determine the feasibility and accuracy of the real-time imaging of contrast echocardiography (MCE) for detecting myocardial perfusion defects at rest and during dobutamine stress echocardiography (DE) compared with 99m Tc MIBI SPECT. The study group consisted of 44 patients (24 men, 20 women, mean age 58.9+/-7.8) with suspected coronary artery disease (CAD). All patients underwent DE. Wall motion (WM) and segmental perfusion were estimated in real time before and at peak stress using a low MI (0.4) after 0.3 ml bolus injections of intravenous Optison. All patients underwent a rest and exercise 99mTc MIBI SPECT study (SPECT). A 16-segment model of the left ventricle was used for the analysis of MP, WM and SPECT by a blinded reviewer. All patients underwent coronary angiography. Significant coronary artery disease was defined as >60% luminal diameter stenosis. RESULTS All patients had significant CAD. Twenty-nine patients had single-vessel and 15 patients had double-vessel disease. For all patients, agreement between MCE and SPECT was 89%, between MCE and WM -86%, and between SPECT and WM -82%. The agreement between MCE and SPECT for LAD, RCA and Cx territories was 81, 91 and 73%, respectively. The sensitivity of MCE and SPECT for detecting perfusion defects due to significant CAD (confirmed angiographically) was 97% and 93%, respectively, and the specificity was 93 and 84%, respectively. CONCLUSION MCE in real-time imaging with Optison has significant potential for the identification of MP abnormalities. MCE correlates very well with SPECT images.

Carotid intima-media thickness, hs-CRP and TNF-α are independently associated with cardiovascular event risk in patients with atherosclerotic occlusive disease

UNLABELLED This prospective study aimed to determine whether carotid intima-media thickness (CIMT) and biomarkers can enhance the predictive value of classic atherosclerosis risk factors (RFs) for cardiovascular (CV) event risk in patients with confirmed atherosclerosis. METHODS Baseline levels of hs-CRP, Tumor Necrosis Factor alpha (TNF-α), Transforming Growth Factor beta (TGF-β), Interleukin-6 (IL-6), Interleukin-10 (IL-10) and Nt-proBNP were measured in 304 subjects (189 men) aged 64.2±9.4 years, with confirmed atherosclerotic occlusive disease. Maximum CIMT values of common, bulb and internal carotid arteries were measured and expressed as mean CIMT value. The incidences of CV death, myocardial infarction (MI), ischemic stroke (IS) and symptomatic lesion progression were recorded. RESULTS During 44.7±12.1 months of follow-up, CV events occurred in 61 (20.1%) patients. Age (odds ratio: OR=1.04; p=0.013), diabetes (OR=2.01; p=0.007), LDL-cholesterol>3.35mmol/L (OR=2.03; p=0.007), previous MI (OR=2.14; p=0.003) and previous IS (OR=3.35; p<0.001) were found independent CV event RFs. Adding biomarkers or CIMT to classic RFs revealed that levels of TNF-α>6pg/mL (OR=1.77; p=0.024), hs-CRP>6mg/L (OR=1.69; p=0.009) or CIMT>1.25mm (OR=5.11; p<0.001) were independently associated with CV event risk. While Nt-proBNP was found RF of CV death (OR=1.19; p=0.003) and MI (OR=1.19; p=0.002). In patients with RFs plus TNF-α>6pg/mL and hs-CRP>6mg/L, a 2- and 5-year event-free survival was 8% and 4%, respectively, as compared to 42% and 33% in those with RFs but lower TNF-α and hs-CRP levels. While, CIMT<1.25mm increased a 2- and 5-year CV event-free survival probability to 79% and 73%, respectively, despite classic RFs presence. CONCLUSION Additive value of TNF-α, hs-CRP and CIMT to classic RFs in CV risk stratification was found in patients with confirmed atherosclerosis. Nt-proBNP was found an independent risk factor of CV death and MI.

Assessment of Flow Changes in the Circle of Willis after Stenting for Severe Internal Carotid Artery Stenosis

Purpose: To assess flow velocities in the cerebral arteries after carotid artery stenting (CAS) in patients with unilateral versus bilateral lesions and analyze velocities in patients with neurological complications after CAS. Methods: Ninety-two patients (68 men; mean age 63.2±8.4 years, range 44–82) with internal carotid artery (ICA) stenoses were divided according to unilateral (group I, n=72) or bilateral (group II, n = 20) disease. Fifty age- and gender-matched patients without lesions in the extra- or intracranial arteries served as a control group. Transcranial color-coded Doppler ultrasound was performed prior to and within 24 hours after CAS in the test groups; systolic velocities were assessed ipsilateral (i) and contralateral (c) to the CAS site in the middle cerebral artery (MCA) and anterior cerebral artery (ACA). Results: Collateral flow via the anterior communicating artery (ACoA) was found in all group-II patients and 90% of group-I patients. After CAS, collateral flow through the ACoA ceased, and the velocity increased by 26% in the iMCA in group I compared to controls (p<0.001). In group II, iMCA flow increased by 30% (p<0.001) and flow via the ACoA (p<0.001) increased, resulting in normalization of cMCA velocities (p=0.928). In 89 (96.7%) subjects, CAS was uncomplicated. Hyperperfusion syndrome occurred in 2 (2.2%) patients, both with bilateral ICA stenoses; 1 (1.1%) transient ischemic attack was seen in a patient with unilateral disease. In the patients with hyperperfusion syndrome, the MCA velocities were 2.7- and 7.4-fold higher, respectively, versus before CAS and 2-fold higher than in controls. Conclusion: Uncomplicated CAS results in an iMCA velocity increase >25% compared to controls. MCA velocities in hyperperfusion syndrome were greatly increased versus before CAS and in controls.

Multimarker Approach in Discriminating Patients with Symptomatic and Asymptomatic Atherosclerotic Carotid Artery Stenosis

Background and Purpose Several circulating biomarkers have been implicated in carotid atherosclerotic plaque rupture and thrombosis; however, their clinical utility remains unknown. The aim of this study was to determine the role of a large biomarker panel in the discrimination of symptomatic (S) vs. asymptomatic (A/S) subjects in a contemporary population with carotid artery stenosis (CS). Methods Prospective sampling of circulating cytokines and blood lipids was performed in 300 unselected, consecutive patients with ≥50% CS, as assessed by duplex ultrasound (age 47-83 years; 110 with A/S and 190 with S) who were referred for potential CS revascularization. Results CS severity and pharmacotherapy did not differ between the A/S and S patients. The median values of total cholesterol, low-density lipoprotein cholesterol, and lipoprotein(a) did not differ, but high-density lipoprotein (HDL) cholesterol was significantly higher (p<0.001) and triglycerides were lower (p=0.03) in the A/S-CS group than in the S-CS group. Interleukin-6 (IL-6) and high-sensitivity C-reactive protein were higher (p=0.04 and p=0.07, respectively) in the S-CS group. Circulating visfatin, soluble CD 40 receptor ligand, soluble vascular cell adhesion molecule, leptin, adiponectin, IL-1β, IL-8, IL-18, monocyte chemoattractant protein-1, myeloperoxidase, matrix metalloproteinases-8, -9, and -10, and fibrinogen were similar, but tissue inhibitor of matrix metalloproteinases-1 (TIMP) was reduced in S-CS compared to A/S-CS (p=0.02). Nevertheless, incorporation of TIMP and IL-6 did not improve the HDL-cholesterol receiver operating characteristics for S-CS status prediction. S-CS status was unrelated to angiographic stenosis severity or plaque burden, as assessed by intravascular ultrasound (p=0.16 and p=0.67, respectively). Multivariate logistic regression analysis revealed low HDL-cholesterol to be the only independent predictor of CS symptoms, with an odds ratio of 1.81 (95% confidence interval=1.15-2.84, p=0.01) for HDL <1.00 mmol/L (first quartile) vs. >1.37 (third quartile). In S-CS, osteoprotegerin and lipoprotein-associated phospholipase A2 (Lp-PLA2) were elevated in those with recent vs. remote symptoms (p=0.01 and p=0.02, respectively). Conclusions In an all-comer CS population on contemporary pharmacotherapy, low HDL-cholesterol (but not other previously implicated or several novel circulating biomarkers) is an independent predictor of S-CS status. In addition, an increase in circulating osteoprotegerin and Lp-PLA2 may transiently indicate S transformation of the carotid atherosclerotic plaque.

The role of carotid intima-media thickness assessment in cardiovascular risk evaluation in patients with polyvascular atherosclerosis.

UNLABELLED In populational studies, carotid intima-media thickness (CIMT) is a valuable tool in the evaluation of cardiovascular (CV) risk. However, there is not much evidence on the relation between CIMT, and CV events in patients who have already undergone revascularization procedures. AIM To evaluate the relationship between CIMT, atherosclerosis extent and CV event rates in patients with established atherosclerosis. METHODS AND RESULTS Baseline mean-CIMT was assessed in 652 patients, including 195; 191; 112; 29 with angiographic arterial stenosis >or=50% in 1; 2; 3 or 4 territories (coronary, supraaortic, renal and/or lower limb arteries), who underwent revascularization procedure in >or=1 arterial territory, and in 125 control subjects without significant lesions. For CIMT >or=1.25mm (>or=3rd quartile), the sensitivity and specificity of >or=2-territory involvement were 81.6% and 81.9%. CV events occurred in 91(14%) subjects. The Kaplan-Meier 2-year CV event-free survival was 95.6%; 93.1%; 83.8%; 77% in patients with mean-CIMT values in the 1st; 2nd; 3rd and 4th quartile. The independent CV adverse event predictors identified in the multivariate Cox proportional hazard model were: mean-CIMT >or=1.25mm (RR=2.52; CI=1.5-4.24; p=0.001); hs-CRP (RR=1.02; CI=1.0-1.03; p=0.011), claudication (RR=1.58; CI=0.98-2.57; p=0.062), accumulation of >or=4 traditional risk factors (RR=2.02; CI=1.31-3.12; p=0.002), 2-3-vessel coronary artery disease (RR=1.95; CI=1.21-3.14; p=0.006). Inclusion of CIMT into the stratification model significantly improved the prediction of CV event risk (DeltaChi(2)=13.27, p=0.0003). CONCLUSIONS In patients undergoing revascularization procedure(s), CIMT has an important and independent contribution to further CV risk stratification. The mean-CIMT value >or=1.25mm is associated with 2.5-fold increased risk of adverse CV events.

Use of the Parodi Anti-Emboli System and Transient Subclavian Steal for Cerebral Protection during Emergent Vertebral Artery Recanalization

Purpose: To report the use of the Parodi Anti-Emboli System (PAES) for cerebral protection during emergent vertebral artery recanalization. Case Report: A 56-year-old chimney sweep was referred with recurrent episodes of vertigo and gait ataxia. Left vertebral artery (LVA) flow was barely detectable on duplex Doppler, and brain computed tomography revealed a small infarct in the posterior inferior cerebellar artery territory. Angiography showed subtotal ostial stenosis of the LVA with poor distal flow and possible thrombus. Due to a high risk of distal embolization with percutaneous treatment, anticoagulation was initiated, and the lesion was to be re-evaluated in 2 to 3 weeks. However, 2 days later, the patient developed severe, aggravating headache, gait and left-limb ataxia, horizontal nystagmus, and vomiting. Emergent angiography showed a total ostial LVA occlusion. The PAES was employed to elicit a temporary subclavian steal during percutaneous LVA recanalization, thus protecting the brain from embolization. The ostial LVA was successfully recanalized and stented, with immediate symptom cessation. Conclusions: The PAES can be successfully applied in the subclavian artery to prevent distal embolization during emergent vertebral artery recanalization. Since a significant proportion of vertebral strokes are embolic, PAES may play a novel role in the treatment of acute cerebellar stroke.

Long-term outcome of coronary balloon angioplasty in diabetic patients

Diabetes is recognised to increase morbidity and mortality after coronary revascularization. We compared clinical outcomes in mean 5-year-long follow-up of coronary balloon angioplasty in diabetic and non-diabetic patients. We studied 621 patients undergoing elective angioplasty from 1987 to 1996. There were 60 (9.7%) patients with diabetes who were compared with 561 non-diabetic patients. Diabetics were older, more often obese, less frequently were current smokers, and less frequently had hypercholesterolaemia. Diabetic patients in comparison with non-diabetics had lower ejection fraction and more frequently had angioplasty of complex (B2 or C) lesions, but there were no differences between both groups in the other clinical and angiographic risk factors. Clinical success of angioplasty, as well as complications rate were similar in both groups. In follow-up restenosis occurred more frequently in diabetics (46.3 vs. 32.2%, P=0.03), resulting in significantly higher re-intervention rate (50.0 vs. 35.4%, P=0.03). Especially diabetic patients were more frequently referred to CABG (20.4 vs. 9. 9%, P=0.02). There were no significant differences in deaths (1.9 vs. 2.8%) and myocardial infarction (3.7 vs. 4.4%). Diabetics presented worse CCS status at the end of observation (Class 0 and I - 61.1 vs. 74.4%, P=0.037). Angioplasty proved to be a safe procedure in diabetic patients. Despite higher restenosis and re-intervention rate in diabetics, mortality as well as myocardial infarction rate was the same in both groups during mean 5-year follow-up.